Project Summary/Abstract Men who have sex with men (MSM) are disproportionately affected by HIV in Guatemala. While national level adult HIV prevalence is less than 1.0%, the most recent prevalence estimate among MSM is 10.5%. This dramatic HIV disparity suggests that current prevention strategies are not sufficient. Pre-Exposure Prophylaxis (PrEP) with daily tenofovir/emtricitabine safely provides high levels of protection against HIV infection if taken correctly and has expanded the HIV prevention landscape. Global PrEP uptake has been slower than expected, however, and PrEP acceptability among men who have sex with men (MSM) is only 58%1. Promoting PrEP requires innovative, tailored approaches grounded in contextualized understanding of the social context and lived experiences of potential users1,2. Among MSM, multiple levels of intersecting stigma related to HIV and sexual orientation can deter PrEP initiation1?14. PrEP stigma, which includes negative stereotypes of PrEP users as having HIV and/or being irresponsible and promiscuous, also greatly inhibits PrEP acceptability and uptake11,13?24. More research on levels and manifestations of PrEP stigma are needed to inform global PrEP promotion efforts. Mobile Health (mHealth) interventions, in particular smartphone applications (apps), can be used to mitigate stigma. The accessibility, affordability, flexibility, and anonymity of smartphones make them a highly appealing medium for engaging MSM and addressing PrEP stigma. Further, smartphone interventions address issues such as transportation logistics, stigma, and confidentiality, all of which are barriers to sexual health services among MSM in Guatemala6?9. While still a nascent field, early evidence, including work by our team, suggests that smartphone apps can address stigma as a barrier to health promotion among MSM by providing information and cultivating social support25?30. Our community research partner, Colectivo Amigos Contra el SIDA (CAS), opened the first community-based PrEP clinic in Latin America in January 2016 and is now planning to scale up coverage. This scale up creates a crucial need for information on barriers to PrEP acceptability and uptake and a unique opportunity to explore PrEP stigma in the lives of MSM. The proposed R21 aims to assess the role of stigma in PrEP acceptability to inform the design of mHealth PrEP promotion strategies through a bidirectional process of research capacity building with UNC and CAS. In Aim 1, we will determine the association between PrEP stigma and PrEP acceptability among MSM using a mixed methods approach. We will conduct qualitative in-depth interviews (n=20) and a structured survey (n=200) to obtain multiple perspectives on PreP acceptability, PrEP stigma, and smartphone use and preferences. For Aim 2, we will assess how MSM in Guatemala interact in online discussions and exchange social support related to PrEP through online focus groups discussions. For Aim 3, we will evaluate strategies to promote uptake of and engagement with a smartphone app for PrEP uptake. In these discussions we will assess optimal channels and messaging for app dissemination and components within the app to promote engagement.